Jonathan Bertin, Pascal Jalaguier, Corinne Barat, Marc-André Roy, Michel J. Tremblay Exposure of human astrocytes to leukotriene C4 promotes a CX3CL1/fractalkine-mediated transmigration of HIV-1-infected CD4(+) T cells across an in vitro blood-brain barrier model. Virology (2014) April; number 454-455, pages 128-138.
Eicosanoids, including cysteinylleukotrienes (cysLTs), are found in the central nervous system (CNS) of individuals infected with HIV-1. Few studies have
addressed the contribution of cysLTs in HIV-1-associated CNS disorders. The authors demonstrate that conditioned medium from human astrocytes treated with leukotriene C4 (LTC4) increases the transmigration of HIV-1-infected CD4(+) T cells across an in vitro blood-brain barrier (BBB) model using cultured brain
endothelial cells. Additional studies indicate that the higher cell migration is linked with secretion by astrocytes of CX3CL1/fractalkine, a chemokine that has chemoattractant activity for CD4(+) T cells. Moreover, the authors report that the enhanced cell migration across BBB leads to a more important CD4(+) T
cell-mediated HIV-1 transfer toward macrophages. Altogether data presented in the present study reveal the important role that LTC4, a metabolite of arachidonic acid, may play in the HIV-1-induced neuroinvasion, neuropathogenesis and disease progression.
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Research funded by CIHR